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Biomedical subjects

S Ward

Publications and source records attributed to S Ward.

At least 163 records · Page 9Linked to original sources
PubMed1995

The Caenorhabditis elegans spe-26 gene is necessary to form spermatids and encodes a protein similar to the actin-associated proteins kelch and scruin.

Six independent mutations in the Caenorhabditis elegans spe-26 gene cause sterility in males and hermaphrodites by disrupting spermatogenesis. Spermatocytes in mutants with the most severe alleles fail to complete meiosis and do not form haploid spermatids. Instead, these spermatocytes arrest with missegregated chromosomes and mislocalized actin filaments, endoplasmic reticulum and ribosomes. In spite of this arrest some of the nuclei and the organelles that normally transport sperm-specific components to the spermatid mature as if they were in spermatids. The spe-26 gene is expressed throughout the testis in both spermatogonial cells and spermatocytes. It encodes a 570-amino-acid polypeptide, which contains five tandem repeat motifs, each of approximately 50 amino acids. These repeats are similar in sequence to repeats in the Drosophila kelch protein, in the invertebrate sperm protein scruin that cross-links actin filaments, as well as in the mouse and pox virus proteins. The functional importance of these repeat motifs is shown by the fact that five of the spe-26 mutations are in the tandem repeats, and one of the most severe mutations is a substitution in a highly conserved glycine. These results suggest that spe-26 encodes a cytoskeletal protein, perhaps actin binding, which is necessary to segregate the cellular components that form haploid spermatids.

Actins↗
PubMed1995

The effects of a chronic application of chlorpyrifos on the macroinvertebrate fauna in an outdoor artificial stream system: species responses.

An outdoor artificial stream system was used to examine the effects of a chronic application of the organophosphate pesticide chlorpyrifos on the invertebrate fauna of the system. Two replicate streams received chlorpyrifos for 21 days at the high dose (5 micrograms.liter-1) or low dose (0.1 microgram.liter-1) or only the carrier solution with which chlorpyrifos is mixed for commercial sale (1,1,1-trichloroethane and xylene). Streams behaved as replicates with respect to five water quality parameters. Seventy-four nonchironomid and 24 chironomid taxa were recorded during the study. The number of taxa and total invertebrate abundance were significantly reduced by both high and low doses of the pesticide. Shannon-Weaver diversity was also reduced by both high and low doses of the pesticide whereas evenness increased in high dose streams. The individual abundances of 9/36 nonchironomid and 13/19 chironomid taxa were significantly reduced by pesticide application; the abundance of one taxon, the gastropod Physastra, increased. The biomass of periphyton in the streams was affected by changes in the abundance of chironomid grazers and Physastra, and the slow recovery of grazers from mortality due to chlorpyrifos appeared to result in a higher biomass of periphyton in the high dose streams than in controls and low dose streams 21 days after dosing ceased. Inverse relationships between the amounts of fine particulate organic matter (FPOM) and the sum of the numbers of all taxa of collector-gatherers (as well as numbers of four individual taxa) were interpreted as disruption of the processing of FPOM by members of this trophic group following toxic effects of chlorpyrifos. The implications of the study for biological monitoring of the direct and indirect effects of chronic doses of chlorpyrifos on streams are discussed, and the use of chironomid larvae and periphyton in biomonitoring to detect pesticide impacts is particularly recommended.

Analysis of Variance↗
PubMed1995

Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler.

The acute safety of the alternative chlorofluorocarbon-free (CFC-free) propellant HFA-134a from a pressurized metered-dose inhaler (MDI) was assessed in 12 healthy male subjects according to a double-blind, randomized, crossover design. On each of three consecutive days, cumulative doses of 1,2,4,8 and 16 inhalations were administered 30 min apart from one of three MDIs. The three MDIs contained either the HFA-134a CFC-free system without drug (HFA-Placebo), the CFC-free system with salbutamol sulphate (HFA-Salbutamol), or a conventional CFC propellant mixture without drug (CFC-Placebo). Pulmonary function (FEV1, FEF25-75%), cardiovascular performance (heart rate and blood pressure), objective tremor measurements and serum potassium were measured after each incremental dose. Similar responses for pulmonary function, cardiovascular performance, tremor and serum potassium were observed between the HFA-Placebo and CFC-Placebo groups. No statistically significant difference was seen in change from baseline of any parameter between the two propellant systems. The administration of HFA-Salbutamol produced statistically significant dose-related increases in heart rate, systolic blood pressure and tremor and a significant dose-related decrease in serum potassium; these responses were expected based on cumulative doses of active drug. Blood samples for HFA-134a analysis were collected to measure systemic absorption of this propellant. Levels of HFA-134a between 200 and 700 ng.ml-1 were detected in all subjects given the CFC-free system. This study shows that acute inhalation of HFA-134a in a CFC-free system is as safe as a CFC propellant system. Salbutamol sulphate in the CFC-free system can be delivered in a dose-linear fashion, without any noticeable change in the safety profile of active drug.

Adolescent↗
PubMed1995

Plasma neuro-endocrine activity in very elderly subjects and patients with and without heart failure.

Marked neuro-endocrine activation in patients with heart failure indicates a worse prognosis and a greater prognostic benefit from the use of ACE inhibitors. However, although the incidence of heart failure rises rapidly with age, relatively little is known about activation of the renin-angiotensin and sympathetic nervous system in patients with heart failure over the age of 75 years. This study was undertaken to investigate plasma concentrations of neurohormonal variables in elderly patients referred to the cardiac clinic with a presumptive, but unconfirmed, diagnosis of heart failure, and to compare these values to plasma concentrations found in age-matched normal subjects. Fifty patients referred with a diagnosis of heart failure were studied. All were receiving a diuretic but not an ACE inhibitor. Patients with renal, haematological and valve disease were excluded. Routine biochemistry and neurohormonal measurements were performed at their first visit, together with an electrocardiogram, chest X-ray and a full clinical examination by an experienced cardiologist. An echocardiogram and Doppler study was also performed and the diagnosis of heart failure either confirmed or refuted. Plasma concentrations of neuro-endocrine variables in healthy elderly subjects were similar to our normal laboratory range in younger subjects with the exception of atrial natriuretic peptide (ANP) (40 +/- 6 pg.ml-1, normal range < 40) and noradrenaline (5.7 +/- 0.7 nmol.l-1, normal range < 2.8). Impairment of left ventricular systolic function was confirmed in 38 of the 50 symptomatic patients (76%) and was associated with increases in plasma concentrations of active renin (58 +/- 8 IU.mol-1, P < 0.001 compared to healthy elderly subjects), angiotensin II (23 +/- 5 pg.ml-1, P < 0.008), noradrenaline (7.7 +/- 1.2 nmol.l-1, P < 0.01) and atrial natriuretic peptide (121 +/- 18 pg.ml-1, P < 0.002). Plasma concentrations were similar in normal subjects and those receiving treatment for heart failure but in whom the diagnosis was not confirmed. A weak relationship between plasma atrial natriuretic peptide (ANP) and left ventricular fractional shortening was demonstrated (r = -0.5, P < 0.001). Using an upper limit of ANP in the healthy elderly subjects of 62 pmol.ml-1 (mean + SD), plasma concentrations of ANP in the population with suspected heart failure had a sensitivity of 74% and specificity of 66% for the diagnosis of heart failure among elderly patients in the community or where access to echocardiography is limited. Left ventricular diastolic filling (assessed by Doppler) was abnormal in healthy elderly subjects and patients with heart failure, and appeared of limited value in the diagnosis of heart failure secondary to diastolic dysfunction. This study confirms that the renin-angiotensin system is activated in elderly patients with heart failure treated with diuretics. ANP may be helpful in diagnosing heart failure where it appears to have a complimentary role to echocardiography.

Aged↗
PubMed1995

Migration of cultured bovine trabecular meshwork cells to aqueous humor and constituents.

PURPOSE: To investigate the migration of cultured bovine trabecular meshwork cells to aqueous humor and some of its constituents, and to compare the migration of normally proliferating and growth-arrested cells. METHODS: Cellular migration was evaluated in 48-well microchemoattraction chambers, and the chemoattractants used were bovine aqueous humor, glycoproteins, and growth factors. RESULTS: The meshwork cells responded well to bovine aqueous humor, and antibody neutralization experiments showed that fibronectin accounted for approximately 40% of aqueous chemoattraction. The glycoproteins laminin, thrombospondin, and transferrin elicited only modest migratory activity. Platelet-derived growth factor was the most powerful chemoattractant of the growth factors tested, and the others produced moderate migratory effects. Basic fibroblast growth factor was not chemoattractive on its own but stimulated migration when combined with heparin. Growth-arrested cells showed less migration to a standardized chemoattractive stimulus than did proliferating meshwork cells. CONCLUSIONS: For the first time, aqueous humor was shown to act as a migratory stimulus for meshwork cells in vitro. The major attractant is fibronectin; the remaining active constituents must still be identified.

Animals↗
PubMed1994

Improving undergraduate biology education in a large research university.

The campus-wide Undergraduate Biology Research Program (UBRP) at the University of Arizona improves undergraduate science education by expanding student opportunities for independent research in faculty laboratories. Within the supportive community of a research laboratory, underclassmen, nonscience majors, and those aspiring to scientific careers all learn to appreciate the process of science. The Program impacts more than the students, promoting departmental cooperation, interdisciplinary collaborations, and improvements in undergraduate science education throughout a Research I University.

Adult↗
PubMed1994

Expression of epidermal growth factor receptor in invasive transitional cell carcinoma of the urinary bladder. A multivariate survival analysis.

Epidermal growth factor receptor (EGFR) immunoreactivity was evaluated in 85 cases of invasive transitional cell carcinoma of the bladder. The impact of EGFR staining on patient survival was compared with tumor stage, histologic grade, immunoreactivity for c-erb B-2 and proliferating cell nuclear antigen, flow cytometrically determined S-phase fraction and DNA ploidy, abnormal expression of blood-group-related antigens, and patient blood type. Using a new monoclonal anti-EGFR antibody reactive in formalin-fixed tissue, the authors found a significant correlation between EGFR expression and high tumor stage, and between EGFR expression and poor patient outcome. However, EGFR expression as a predictor of prognosis was not independent of stage. An intriguing association between patient blood type and patient survival was noted. Other indices did not predict patient outcome after data were adjusted for stage.

ABO Blood-Group System↗
PubMed1994

Assessing the viability of mutant and manipulated sperm by artificial insemination of Caenorhabditis elegans.

We describe a protocol for artificial insemination of Caenorhabditis elegans which we used to evaluate the viability of sperm from different strains and of sperm activated in vitro. Worms can be artificially inseminated with almost 100% success. Both male and hermaphrodite sperm can be used for insemination. Sperm from a sterile hermaphrodite [fem-3(q23ts)] were found to be viable. As with normal mating, male sperm inseminated into hermaphrodites artificially outcompete the hermaphrodite's own sperm, even though they have not been ejaculated with seminal fluid. Spermatozoa that were activated in vitro from spermatids by the weak base triethanolamine were viable. In contrast, spermatozoa activated in vitro by protease treatment were not.

Animals↗
PubMed1994

Cancer pain: knowledge, attitudes of pharmacologic management.

The knowledge of, attitudes toward, and perceived barriers to pharmacologic management of cancer pain were compared between oncology nurses (N = 128) and long-term care facility (LTCF) nurses (N = 72) using an 82-item questionnaire. The oncology nurses were significantly more knowledgeable about pharmacologic management of cancer pain than were the nurses in LTCFs. However, the two groups did not differ in their attitudes toward pain management, with the exception that nurses in LTCFs were more likely to believe that patients over-report their pain. LTCF nurses were more likely than the oncology nurses to believe that inadequate assessment of pain, lack of equipment, and lack of skills to use equipment were impediments to pain management.

Adult↗
PubMed1994

Development of cross-tolerance between delta 9-tetrahydrocannabinol, CP 55,940 and WIN 55,212.

In previous studies it was shown that the structurally dissimilar compounds delta 9-THC, CP 55,940 and WIN 55,212 produced more or less the same pharmacological effects and interacted with the same cannabinoid receptor. However, their potencies vary across a number of pharmacological assays, suggesting that a single mechanism may not account for all of their actions. To further explore possible differences among these cannabinoids, cross-tolerance studies were conducted. Specifically, the ability of delta 9-THC, CP 55,940 and WIN 55,212 to produce hypoactivity, hypothermia, antinociception and catalepsy was assessed in mice that had been chronically treated with either delta 9-THC or CP 55,940. The results indicated the delta 9-THC-treated mice were tolerant to delta 9-THC. The degrees of tolerance were 15.9, 7.8, and 13.4 for spontaneous activity, hypothermia and antinociception, respectively. Mice chronically treated with delta 9-THC also exhibited tolerance to some of the behavioral effects of CP 55,940 and WIN 55,212. The tolerance induced by repetitive administration of CP 55,940 was substantial. The ED50 for CP 55,940 was shifted 102 fold for spontaneous activity, 100 for hypothermia and 44 for catalepsy. Also, some cross-tolerance to delta 9-THC and WIN 55,212 was observed in CP 55,940 chronically treated mice. These findings indicate that cross-tolerance develops between delta 9-THC, CP 55,940 and WIN 55,212 and that these agents have some actions in common. However, quantitative differences in their development of cross-tolerance suggests that all of their actions may not be identical.

Analgesics↗
PubMed1994

Concerns about reporting pain and using analgesics. A comparison of persons with and without cancer.

Cancer pain is not adequately managed, and patients' reluctance to report pain and to use analgesics contribute to this problem. The Barriers Questionnaire (BQ) assesses eight patient concerns about reporting pain and using analgesics. This study was designed to determine (a) whether such concerns differ for persons who have cancer versus those who do not, (b) whether the BQ has test-retest reliability, and (c) whether concerns are related to reticence in reporting pain and using analgesics. Two groups, 53 adults with cancer and 40 without, completed the BQ twice at a 1-week interval. The BQ has eight subscales (e.g., concerns about addiction) and a total scale score (alpha = 0.89). There were no differences between persons with and without cancer on BQ total or subscale scores. Test-retest reliability of the total scale was r = 0.90, whereas the subscales showed r = 0.60-0.81. At Time 1, 16% said they hesitated to report pain, and 12% hesitated to use analgesics; at Time 2, 15% hesitated to report pain, and 10% hesitated to use analgesics. At Time 2, those who hesitated to report pain had higher BQ total scores than those who did not hesitate to report it (p < 0.05). We discuss the results of this study with respect to patient and public education.

Adult↗
PubMed1993

Influence of gestodene and desogestrel as components of low-dose oral contraceptives on the pharmacokinetics of ethinyl estradiol (EE2), on serum CBG and on urinary cortisol and 6 beta-hydroxycortisol.

A randomized controlled clinical trial was undertaken over a 6-month treatment period with two low-dose combined oral contraceptives (OC) to investigate whether the metabolism and elimination of ethinyl estradiol (EE2) is differently influenced by the two progestational components gestodene (G) and desogestrel (D), an issue which has been very controversial recently. The two formulations contained 30 micrograms EE2 each, together with either 75 micrograms G or 150 micrograms D. Of the 40 young women recruited for each formulation, 31 of each group were available for statistical evaluation. The pharmacokinetics of serum EE2 were studied on day 1, 10 and 21 of cycle 1, 3 and 6. There were no significant differences between the two groups in any cycle with respect to parameters measured. This was true for the distinct intracyclical rise in the mean EE2 serum levels from day 1 to day 10 and the smaller further increase between day 10 and day 21, with no change in this respect between the cycles studied. Respective changes were seen with regard to the area under the EE2 serum concentration curve up to 4 and 24 hours (AUC0-4 and AUC0-24), cmax and tmax of serum EE2. The estrogen-dependent corticoid-binding globulin (CBG) increased similarly in the two groups intracyclically and slightly also intercyclically at all times tested. Except for the first treatment cycle, urinary excretion of cortisol and 6 beta-hydroxycortisol displayed a tendency to lower values intracyclically as well as intercyclically, again with no differences between the two groups. Also, the 6 beta-hydroxycortisol-to-cortisol ratio was not different between the groups, showing a slight tendency to rise from about 4 at the beginning of the medication to around 5.5 at the end of the 6th treatment cycle in both groups. It is concluded that G and D as components of low-dose OCs exert comparable effects on the metabolism and elimination of EE2.

Adult↗